Cardiac Metabolic Effects Research Articles

Cardiac metabolic effects of KNa1.2 channel deletion and evidence for its mitochondrial localization.

Controversy surrounds the molecular identity of mitochondrial K+ channels that are important for protection against cardiac ischemia-reperfusion injury. Although KNa1.2 (sodium-activated potassium channel encoded by Kcn2) is necessary for cardioprotection by volatile anesthetics, electrophysiological evidence for a channel of this type in mitochondria is lacking. The endogenous physiological role of a potential mito-KNa1.2 channel is also unclear. In this study, single channel patch-clamp of 27 independent cardiac mitochondrial inner membrane (mitoplast) preparations from wild-type (WT) mice yielded 6 channels matching the known ion sensitivity, ion selectivity, pharmacology, and conductance properties of KNa1.2 (slope conductance, 138 ± 1 pS). However, similar experiments on 40 preparations from Kcnt2-/- mice yielded no such channels. The KNa opener bithionol uncoupled respiration in WT but not Kcnt2-/- cardiomyocytes. Furthermore, when oxidizing only fat as substrate, Kcnt2-/- cardiomyocytes and hearts were less responsive to increases in energetic demand. Kcnt2-/- mice also had elevated body fat, but no baseline differences in the cardiac metabolome. These data support the existence of a cardiac mitochondrial KNa1.2 channel, and a role for cardiac KNa1.2 in regulating metabolism under conditions of high energetic demand.-Smith, C. O., Wang, Y. T., Nadtochiy, S. M., Miller, J. H., Jonas, E. A., Dirksen, R. T., Nehrke, K., Brookes, P. S. Cardiac metabolic effects of KNa1.2 channel deletion and evidence for its mitochondrial localization.

Sex differences in myocardial metabolism and cardiac function: an emerging concept

There is substantial evidence that there are dramatic sex-related differences in the incidence of cardiovascular disease, apparently related to the presence of steroid hormones. This is supported by the discovery of steroid hormone receptors in the heart and vasculature. More controversial is the area of sex-related differences in cardiac metabolism and function. A number of human and animal studies have demonstrated that estrogen and testosterone have cardiac metabolic effects. Additionally, research shows females have higher heart rates and various indices of function, including cardiac output and stroke volume, compared with males. However, some controversy exists, as other studies report that function in isolated muscle preparations is lower in females versus males. The reasons for these differences may reflect effects of sex hormones that are dependent on the conditions being studied. Cardiac function is reduced in postmenopausal females, suggesting that female sex hormones, specifically estrogen and progesterone, influence cardiac function. Apart from its well-documented vasodilatory effects, estrogen has also been shown to have negative inotropic effects and to reduce Ca(2+) transients in cardiomyocytes. Similar results have been found for progesterone. Several studies show that testosterone administration appears to increase cardiac performance, while others show that it increases the stiffness of the ventricle due to increased collagen synthesis, thereby reducing diastolic performance. This review will discuss current evidence suggesting sex-related differences in cardiac metabolism and its energetics and function and will present the potential role of the principal sex steroid hormones.

Is DDD pacing superior to VVI,R? A study on cardiac sympathetic nerve activity and myocardial oxygen consumption at rest and during exercise.

Rate responsive ventricular pacing (VVI,R) has been demonstrated to equal atrial synchronous ventricular pacing (DDD) with regard to hemodynamics and exercise tolerance. Whether the two modes are also comparable, with regard to cardiac metabolic effects, is not yet clear. We assessed central hemodynamics, cardiac sympathetic nerve activity (cardiac norepinephrine overflow), and myocardial oxygen consumption in 16 patients treated with rate responsive atrial synchronous ventricular pacemakers (DDD,R) due to high degree AV block. The study was performed at rest and during supine exercise at two workloads (30 +/- 12 and 68 +/- 24 watts, respectively) during VDD and rate matched VVI pacing (VVIm). Ventricular rates at rest and during both workloads were almost identical. Cardiac output at rest tended to be higher in the VDD mode, due to a slightly higher stroke volume. Central pressures including right atrial pressure and pulmonary capillary wedge pressure were similar in the pacing modes. The coronary sinus blood flow, the coronary sinus arteriovenous oxygen difference, and the myocardial oxygen consumption did not differ between the two pacing modes. Cardiac norepinephrine overflow was similar in the two pacing modes, at rest or during exercise. Thus, we found no significant differences between VDD and VVIm pacing with regard to central hemodynamics, cardiac sympathetic nerve activity (cardiac norepinephrine overflow), or myocardial oxygen consumption either at rest or during moderate exercise.

Cardiac metabolic effects of heparin differentiate between patients with normal and stenotic coronary arteries

We studied the effects of heparin, given as 12,500 units intravenously, on cardiac metabolism during catheterization of the coronary sinus at rest and during repeated rapid atrial pacing in 8 patients with stable angina pectoris, positive stress tests and coronary arterial disease and in 8 patients with normal coronary arteries without objective signs of ischemic heart disease. Heparin did not influence angina, ST-segment depression or myocardial lactate production induced by pacing in the group with diseased coronary arteries. In both groups, heparin increased the arterial levels (70%) and the myocardial uptake (40–50%) of free fatty acids, the latter only during non-ischemic conditions. Myocardial net uptakes of glucose, lactate and glutamate and the release of alanine were reduced by heparin in the subjects with normal coronary arteries but not in those with ischemic heart disease. Myocardial oxygen consumption was unchanged. In the patients with normal coronary arteries, the levels of free fatty acid in the arteries were positively related to myocardial uptake of fatty acids and the release of citrate but inversely related to cardiac uptake of lactate and glucose. These relations were lacking in the patients with diseased coronary arteries. The metabolic effects of heparin on the heart, therefore, were diminished in patients with ischemic heart disease when compared to controls. This is probably due to an altered regulation of substrate preference in ischemic hearts.

Antianginal and cardiac metabolic effects of low-dose glucose infusion during pacing in patients with and without coronary artery disease

Anginal threshold and cardiac metabolism during infusion of glucose, 350 mg/min, were compared with control values before, during, and after pacing in nine patients with coronary artery disease (CAD) and nine patients without coronary artery disease (non-CAD). Pacing induced no ischemia in non-CAD patients; in CAD patients, intolerable angina developed in less than 5 minutes. However, glucose infusion in the latter group increased the time to onset of angina (110 ± 24 seconds before infusion versus 140 ± 24 seconds following infusion) and decreased the extent of ST segment depression (1.8 ± 0.3 mm before infusion versus 0.9 ± 0.2 mm following infusion, p < 0.01) following pacing. In all subjects, arterial levels and cardiac uptake of glucose rose by 100% ( p < 0.001) and those of free fatty acids fell by 50% ( p < 0.01). Arterial lactate and uptake of lactate by nonischemic myocardium increased by 30% ( p < 0.05). During pacing in CAD patients, this elevated uptake was outweighed by similar increases of lactate release from ischemic areas, leaving mean negative global exchanges unaltered. In CAD patients solely, rebuilding of cardiac glycogen after pacing was suggested from augmented citrate efflux in the control period but not during glucose infusion, suggesting a glycogen-sparing effect. Arterial concentrations and net cardiac fluxes of oxygen, glutamate, and alanine remained unaltered. In conclusion, beneficial effects of glucose during ischemia are associated with increased aerobic and anaerobic glycolysis, saving of glycogen, and decreased lipolysis.

Haemodynamic and cardiac metabolic effects of the new beta 1 agonist prenalterol in patients with cardiac failure.

Prenalterol, a beta 1 selective agonist, exerts a positive inotropic action in animal studies as well as in human volunteers and is effective when administered orally. To assess its immediate haemodynamic and myocardial metabolic effects, we studied the response to prenalterol (50 and 100 micrograms kg-1 given intravenously by cardiac catheterization) in 15 patients with congestive heart failure secondary to coronary artery disease or non-ischaemic cardiomyopathy. At peak effect, cardiac index increased from 2.6 +/- 0.5 to 3.2 +/- 0.8 l min-1 m2 (mean +/- S.D.) (P less than 0.001); peak rate of left ventricular pressure development rose from 963 +/- 242 to 1335 +/- 411 mmHg s-1 (P less than 0.001); left ventricular end-diastolic pressure fell from 25 +/- 6 to 17 +/- 7 mgHg (P less than 0.001); coronary sinus blood flow increased from 113 +/- 39 to 148 +/- 55 ml min-1 (P less than 0.01); myocardial oxygen consumption was augmented from 12.7 +/- 3.9 to 16.4 +/- 5.8 ml min-1 (P less than 0.001); and heart rate increased slightly (from 76 +/- 12 to 86 +/- 14 beats min-1; (P less than 0.05)). No significant changes occurred in left ventricular systolic pressure, stroke volume index, myocardial lactate extraction rate and myocardial arteriovenous oxygen difference, and no patients developed angina, ECG changes or ventricular arrhythmias. Infusion of prenalterol effectively improved haemodynamic function and cardiac metabolism in cardiomyopathy. Therefore this agent deserves further investigation to evaluate its possible role for the long-term therapy of patients with chronic heart failure.

Hemodynamic and cardiac metabolic effects of inotropic stimulation with dobutamine in patients with coronary artery disease.

The hemodynamic and myocardial metabolic effects of two intravenous doses (5 and 10 ug/kg/min) of dobutamine were measured in 15 patients with congestive heart failure secondary to coronary artery disease. Dobutamine at 5 μg/kg/min induced an increase in peak rate of left ventricular pressure rise (dp/dtmax) from 1004 ± 261 to 1386 ± 469 mm Hg × s−1, coronary sinus blood flow (CSF) from 98 ± 34 to 128 ± 60 ml/min and myocardial oxygen consumption (MVO2) from 10.5 ± 3.8 to 14.3 ± 6.9 ml/min. It decreased mean left ventricular end-diastolic pressure (LVEDP) from 24 ± 6 to 20 ± 8 mm Hg. All changes were significant ( P < 0.01). No significant changes occurred in mean heart rate, left ventricular systolic pressure, arterio-coronary venous oxygen content difference and mean myocardial lactate extraction rate. Dobutamine at 10 μg/kg/min further increased dp/dtmax to 1545 ± 408 mm Hg × s−1, CSF to 146 ± 75 ml/min and MVO2 to 17 ± 9.1 ml/min. Because mean heart rate also increased significantly from 73 ± 15 to 90 ± 23 beats/min it is possible that the concomitant increase in myocardial oxygen demand was no longer offset by the reduction in preload (further decrease of LVEDP to 18 ± 7 mm Hg). Thus, myocardial oxygen demand was inadequately met, myocardial lactate extraction rate decreased significantly (34 ± 16 to 14 ± 20%, P < 0.01) and signs of myocardial ischemia developed in three of the 15 patients. For this reason, heart rate should be monitored closely if dobutamine is given to patients with limited capacity to increase myocardial blood flow and oxygen delivery to the myocardium.

Hemodynamic and cardiac metabolic effects of diastolic intraaortic balloon obstruction combined with distal aortic “booster” occlusion in experimental acute myocardial infarction with shock

Hemodynamic and cardiac metabolic effects of diastolic intraaortic balloon obstruction combined with distal aortic “booster” occlusion in experimental acute myocardial infarction with shock

Effects of isoproterenol on hemodynamic alterations, myocardial metabolism, and coronary flow in experimental acute myocardial infarction with shock

Hemodynamic and cardiac metabolic effects were investigated in dogs given isoproterenol (2 to 6.6 μg per minute) and in those receiving no therapy, following production of acute myocardial infarction with shock by plastic sphere coronary embolization. Following coronary embolization, before therapy, there were significant declines in cardiac output, aortic pressure, coronary sinus flow, and left ventricular mechanical efficiency. Left ventricular “excess lactate” was produced in almost all animals. After 15 minutes of isoproterenol infusion, there were slight increases of cardiac output, heart rate, left ventricular work, coronary flow, and left ventricular oxygen consumption. Left atrial and aortic pressures, left ventricular mechanical efficiency, and “excess lactate” production were unchanged. Systemic and coronary vascular resistances declined moderately. With continued infusion, for one hour, cardiac output, aortic pressure, and coronary sinus flow declined to levels obtained prior to infusion and left ventricular “excess lactate” production increased further. There was progressive decline of arterial pH. In comparison to those receiving no therapy, isoproterenol-treated animals had significantly lower systemic and coronary vascular resistances and greater left ventricular “excess lactate” production. It is concluded that isoproterenol produces moderate initial hemodynamic improvement in acute myocardial infarction with shock, but this is not sustained and left ventricular “excess lactate” production is unfavorably affected. It is suggested that lack of significant sustained hemodynamic improvement and continued anaerobic metabolism with isoproterenol therapy in acute myocardial infarction with shock most probably results from failure to raise the critically low coronary perfusion pressure sufficiently to produce adequate oxygenation of the acutely ischemic left ventricle.

Comparison of the hemodynamic and cardiac metabolic effects of isoproterenol and norepinephrine in experimental acute myocardial infarction with shock

Comparison of the hemodynamic and cardiac metabolic effects of isoproterenol and norepinephrine in experimental acute myocardial infarction with shock

Mechanical increase of vascular resistance in experimental myocardial infarction with shock.

The hemodynamic and cardiac metabolic effects of increasing central aortic pressure by obstructing the abdominal aorta with a balloon catheter introduced via a femoral artery were determined in 28 anesthetized dogs with acute myocardial infarction and shock produced by coronary embolization with plastic spheres. Following coronary embolization, aortic pressure, cardiac output, and left ventricular mechanical efficiency declined in all animals; left ventricular "excess lactate" appeared in about one-half. With abdominal aortic obstruction for 1 hour, there were significant elevations of postembolic aortic pressure, coronary flow, cardiac output, left ventricular oxygen consumption and mechanical efficiency. Left atrial pressure rose slightly but not beyond normal limits. Arterial-coronary sinus oxygen difference diminished, and left ventricular excess lactate diminished or disappeared in 60% of the animals in which it was noted in the postembolic state. After 1 hour of abdominal aortic obstruction, cardiac output, central aortic pressure, and coronary flow diminished moderately. It is concluded that mechanical increase of vascular resistance for periods up to 1 hour may improve myocardial performance in acute myocardial infarction with shock. The increased left ventricular oxygen needs are met adequately by the increase of coronary flow associated with the increase of perfusion pressure.

Hemodynamic and Cardiac Metabolic Effects of Increasing Coronary Flow by Mechanical Increase of Vascular Resistance in Acute Myocardial Infarction with Shock.

s1 May 1966Hemodynamic and Cardiac Metabolic Effects of Increasing Coronary Flow by Mechanical Increase of Vascular Resistance in Acute Myocardial Infarction with Shock.Leslie A. Kuhn, M.D., F.A.C.P., Howard J. Kline, M.D., Robert I. Hamby, M.D., Anthony J. Marano Jr., M.D., Lawrence J. Cohn, M.D., Marvin Berger, M.D.Leslie A. Kuhn, M.D., F.A.C.P.Search for more papers by this author, Howard J. Kline, M.D.Search for more papers by this author, Robert I. Hamby, M.D.Search for more papers by this author, Anthony J. Marano Jr., M.D.Search for more papers by this author, Lawrence J. Cohn, M.D.Search for more papers by this author, Marvin Berger, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-64-5-1155_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn an attempt to improve myocardial performance in acute myocardial infarction with shock, increments of coronary perfusion pressure were achieved by partial obstruction of the abdominal aorta with a balloon catheter introduced via a femoral artery in 28 dogs with plastic sphere coronary embolization. Alterations of central aortic pressure, coronary sinus flow, cardiac output, left atrial pressure, left ventricular work, left ventricular oxygen consumption, coronary vascular resistance, left ventricular mechanical efficiency, and left ventricular lactate and pyruvate extraction were determined before and after coronary embolization and at intervals during 1 hour of abdominal aortic obstruction. After coronary embolization, aortic pressure,... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1966Volume 64, Issue 5Page: 1155-1155KeywordsAcute myocardial infarctionCathetersCoronary arteriesFemoral arteriesHemodynamicsLactatesMyocardial infarctionOxygen consumptionPyruvateShock Issue Published: 1 May 1966 PDF downloadLoading ...

The hemodynamic and cardiac metabolic effects of increasing coronary flow by mechanical increase of vascular resistance in acute myocardial infarction with shock

The hemodynamic and cardiac metabolic effects of increasing coronary flow by mechanical increase of vascular resistance in acute myocardial infarction with shock